DESCRIPTION: Intra-mitochondrial Ca is a key signal transducer for energy metabolism. In the heart Ca controls the cyclic contraction, which uses the majority of cellular ATP. As a consequence, it is important to determine whether cytosolic Ca fluctuations are conveyed to the mitochondria. The long-term objective of the proposal is to elucidate the regulation of intracellular Ca in cardiac cells; in the short term the aim is to employ fluorescence microscopy and electrophysiological recording to investigate the role of mitochondria in the regulation of Ca signalling. The working hypothesis is that mitochondrial Ca is heterogeneous, and mitochondria could respond differentially to Ca fluctuations depending on their membrane potential and spatial location. The specific aims are to determine spatial in-homogeneities in mitochondrial Ca, to assess the ability of mitochondria to transport Ca during changes of cytosolic Ca, and to determine whether there is cross-talk between mitochondria and sarcoplasmic reticulum.